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Introduction: Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization with insulin glargine might improve the levels of these factors. Methods: Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years). Results: Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in the insulin glargine but not in the standard care group. Conclusion: In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments.

Background: A previous cross-sectional study suggested that tissue plasminogen activator–activity might be an early marker of asymptomatic lower extremity arterial disease, but the long-term relationship is unknown. Subjects and methods: This study included 96 diabetic (48 type 1/48 type 2) and 62 non-diabetic subjects aged 30–70 years without previously known lower extremity arterial disease (age: 50.3 ± 9.3 years, gender: M/W 47.5/52.5% and body mass index: 26.6 ± 4.5 kg/m2). The relationships between asymptomatic lower extremity arterial disease and fibrinolytic markers (tissue plasminogen activator–activity, tissue plasminogen activator–mass, plasminogen activator inhibitor-1 activity) at baseline and after 10 years were assessed by logistic regression analysis adjusting for age, hypertension, statin treatment, HbA1c, triglycerides and low-density lipoprotein cholesterol as fixed covariates. Results: The tissue plasminogen activator–activity at baseline and at the 10-year follow-up significantly predicted the presence of sign(s) of lower extremity arterial disease (odds ratio = 1.78, 95% confidence interval: 1.02–3.10, p = 0.043 and odds ratio = 1.78, 95% confidence interval: 1.12–2.23, p = 0.014, respectively). In addition, tissue plasminogen activator–mass at the 10-year follow-up was associated with signs of lower extremity arterial disease (odds ratio = 1.07, 95% confidence interval: 1.00–1.15, p = 0.046). Baseline age, hypertension and HbA1c were independently associated with sign(s) of lower extremity arterial disease at 10 years (odds ratio = 1.09, 95% confidence interval: 1.04–1.14, p = Conclusion: This long-term study supports previous findings of a significant association between asymptomatic lower extremity arterial disease and tissue plasminogen activator–activity. Thus, tissue plasminogen activator–activity may be an early marker of lower extremity arterial disease although the mechanism of this relationship remains unclear.

To explore the role of tissue plasminogen activator (tPA) activity and plasminogen activator inhibitor type 1 (PAI-1) in survivors of a first myocardial infarction (MI). Insulin and proinsulin were analysed as potential risk factors.Case-control study in northern Sweden.A total of 115 patients under 65 years of age with a first MI were enrolled and recalled for further examination 3 months later. Twenty-seven patients were excluded, 17 with known diabetes and 10 who did not come to the follow-up, giving a final number of 88 patients, 73 men and 15 women. Patients were age- and sex-matched with control subjects drawn from the local cohort in the MONICA population survey 1994.We compared MI patients and controls using univariate and multiple regression analyses including odds ratios (OR).PAI-1 activity, fibrinogen, postload insulin and -proinsulin were significantly higher and tPA activity significantly lower in MI patients in the univariate analysis. In a multiple regression analysis, including also age, sex and cardiovascular risk factors, these parameters were divided in quartiles. The lowest quartile of tPA activity was significantly associated with MI (OR = 19.1; CI 3.0-123) together with the highest quartiles of fibrinogen (OR = 25; CI 5.2-120) but other variables were not.Low tPA activity, i.e. low fibrinolytic activity, characterized nondiabetic subjects after a first MI which is not explained by concomitant disturbances in metabolic and anthropometric variables.

Background and Purpose— Several studies indicate a declining case-fatality and mortality in stroke. Little is known about time trends in stroke for subjects with diabetes. The purpose of this study was to compare time trends in incidence, case-fatality and mortality for stroke patients with or without diabetes. Methods— This study was based on the Northern Sweden MONICA Project Stroke registry during 1985 to 2003. 15 382 patients, aged 35 to 74 years, were included in the study. 11 605 had a first-ever stroke and 3777 had a recurrent stroke. In both men and women previously diagnosed diabetes was found in 22.8%. Results— The incidence of stroke was 5 and 8 times higher in diabetic subjects than in nondiabetics, in men and women, respectively. Incidence of first-ever stroke decreased for nondiabetic men, probability value Conclusion— The incidence of stroke declined in both nondiabetic and diabetic subjects except for diabetic men and for nondiabetic women with first-ever stroke. Case-fatality in first-ever stroke declined for all but diabetic women. This led to a decreased mortality over the 19-year period for both groups. This is the first time that the decline in stroke incidence is reported in this MONICA population.

The aim of this study was to compare time trends in incidence, case fatality and mortality due to myocardial infarction (MI) in patients with or without diabetes.This study was based on the Northern Sweden MONICA Project MI registry with a target population of about 200,000 inhabitants in the age group 35--64 years in the two northernmost counties of Sweden. During 1989--2000, 6254 patients who had had an MI according to MONICA criteria were included in this study: 4569 patients had a first MI and 1685 had a recurrent MI. Sixteen per cent of the men and 20% of the women had had diabetes mellitus diagnosed prior the MI.Over the 12-year period, there was a declining trend in incidence and case fatality in first MI. Also, the event rates (first ever and recurrent MI) declined in men without diabetes. In women without diabetes favourable time trends were seen in first ever MI, recurrent MI and in case fatality. There were no favourable time trends for any of these outcomes in patients with diabetes.In nondiabetic subjects below the age of 65, the incidence of, and case-fatality in, MI declined. This led to a decreased mortality over the 12-year period. These favourable trends over time were not observed in diabetic subjects.